Project Summary/Abstract Suicide is the second leading cause of death among adolescents, and nationally representative data indicate 29% of sexual minority adolescents (SMAs) have attempted suicide during the past year. Alarmingly high rates of suicidal behavior in this population can be attributed, in part, to gay-related bullying experienced by SMAs and higher rates of childhood abuse among SMAs. However, mechanisms underlying the association between psychosocial factors and suicidality among SMAs remain unstudied. The proposed investigation will examine biological mechanisms of suicidal behavior among SMAs. Researchers have recently identified biological mechanisms which distinguish individuals who are at risk for engaging in suicidal behavior, including low hair cortisol concentrations (HCC) and high levels of inflammatory biological markers. Biological mechanisms have high potential to partially explain suicidal behavior disparities between SMAs and non-SMAs, as individuals who experience bullying and childhood abuse are more likely to evidence biological dysregulation during adolescence and into adulthood. The proposed K01 study will examine how biological mechanisms (HCC and inflammatory markers) are associated with gay-related bullying, and how biological mechanisms predict clinical and neurocognitive correlates of suicidal behavior (suicidal ideation, impulsivity, and decision-making) among SMAs and non-SMAs. The proposed study will be the first in a program of research designed to facilitate more effective identification of SMAs at risk for suicidal behavior and identify psychosocial, biological, and neurocognitive factors which can be targeted within interventions designed to attenuate stark disparities in suicidal behavior between SMAs and non-SMAs. To launch this program of research, the candidate will augment his prior training in social and behavioral determinants of SMA health with training in biological mechanisms of suicidal behavior, conducting longitudinal research and analyzing longitudinal data, and neurocognitive correlates of suicidal behavior. He has an ideal mentorship team within an optimal scientific training environment to undertake the proposed research and training plans. Primary Mentor Dr. Nadine Melhem has significant expertise in biological mechanisms of suicidal behavior and longitudinal research methods. Co-Mentor Dr. Michael Marshal is an expert on SMA mental health disparities, including suicidality. The candidate will also receive mentoring from internal Consultant Dr. Anna Marsland, a leading scholar in psychoneuroimmunology, internal Consultant Dr. Kehui Chen, a statistician with ongoing collaborations with Dr. Melhem, and external Consultant Dr. Jeffrey Bridge, who contributes expertise in neurocognitive risk for suicidal behavior among adolescents. Completion of the proposed research and training plans will position the candidate as a leading scholar in SMA suicidal behavior, preparing him to examine this pressing mental health disparity longitudinally across adolescence and at multiple levels of analysis.